The broad objective of the proposed research is to advance our knowledge on the epidemiology of arena viruses associated with rodents native to the southern United States. Knowledge of the rodent host relationship (including duration and magnitude of virus shedding in infected rodents) and geographical distribution of infected rodents is essential to an accurate understanding of the human diseases caused by arena viruses. Recent studies provided the first unequivocal evidence that arena viruses are geographically widely distributed u the southern U.S. in associateion with rodents belonging to the genera Neotome, Peromyscus and Sigmodon. The specific aims of the proposed research are to: 1) Extend our knowledge on the geographic range, rodent host relationship, genotypic diversity off arena viruses naturally associated with signodontine rodents in the southern U.S.; 2) refine our knowledge on the ecology of Whitewater Arroyo (WWA) and Bear Canyon (BCN) viruses; 3) investigate the pathogenesis of WWA and BCN viruses inb their principal rodent hosts (Neotoma and Permyscus rodents, respectively); 4) assess whether knowledge of the phylogenetic history of North American rodents can be used to accurately predict the geographic range and rodent host associations of the various area viruses indigenous to the southern U.S.; and, 5) investigate further the human health significance of North American rodent-borne arena viruses.